Modulating cell response on cellulose surfaces; tunable attachment and scaffold mechanics

Abstract

Combining surface chemical modification of cellulose to introduce positively charged trimethylammonium groups by reaction with glycidyltrimethylammonium chloride (GTMAC) allowed for direct attachment of mammalian MG-63 cells, without addition of protein modifiers, or ligands. Very small increases in the surface charge resulted in significant increases in cell attachment: at a degree of substitution (DS) of only 1.4%, MG-63 cell attachment was [ 90% compared to tissue culture plastic, whereas minimal attachment occurred on unmodified cellulose. Cell attachment plateaued above DS of ca. 1.85% reflecting a similar trend in surface charge, as determined from f-potential measurements and capacitance coupling (electric force microscopy). Cellulose film stiffness was modulated by cross linking with glyoxal (0.3-2.6% degree of crosslinking) to produce a range of materials with surface shear moduli from 76 to 448 kPa (measured using atomic force microscopy). Cell morphology on these materials could be regulated by tuning the stiffness of the scaffolds. Thus, we report tailored functionalised biomaterials based on cationic cellulose that can be tuned through surface reaction and glyoxal crosslinkin?g, to influence the attachment and morphology of cells. These scaffolds are the first steps towards materials designed to support cells and to regulate cell morphology on implanted biomaterials using only scaffold and cells, i.e. without added adhesion promoters.Electronic supplementary material The online version of this article (https://doi

Mechanically robust cationic cellulose nanofibril 3D scaffolds with tuneable biomimetic porosity for cell culture

“…In common with most reactive crosslinkers, unreacted glyoxal is cytotoxic, but once reacted to form acetal and hemiacetal linkages with cellulose, does not inhibit cell viability. 63 This modification served to support the delicate structures, maintaining the integrity of the vascularised or porous internal architecture, but it has also been shown previously that crosslinking further increases the spreading of attached MG-63 cells on cationised cellulose scaffolds. 63 Furthermore, modification of the mechanical properties of the scaffold can act as a stimulus to up-regulate physiological processes and signalling pathways within the cell cycle, thus promoting cell growth.…”

“…63 This modification served to support the delicate structures, maintaining the integrity of the vascularised or porous internal architecture, but it has also been shown previously that crosslinking further increases the spreading of attached MG-63 cells on cationised cellulose scaffolds. 63 Furthermore, modification of the mechanical properties of the scaffold can act as a stimulus to up-regulate physiological processes and signalling pathways within the cell cycle, thus promoting cell growth. 65,66 Thus, these materials could serve as very flexible scaffolds, allowing external shape/size, internal architecture, rigidity and robustness to be varied while also offering opportunities to modulate cell response, as described later.…”

Controlling Cell Behavior through the Design of Biomaterial Surfaces: A Focus on Surface Modification Techniques

“…Of significance, the surface charge can also contribute in encapsulation of drugs, growth factors, or NPs into scaffolds . Courtenay et al incorporated the cationic trimethylammonium groups on the surface of cellulose scaffold by reaction with glycidyltrimethylammonium chloride and investigated the attachment of MG‐63 cells . They reported that a very small increase in the surface charge, without addition of any protein modifiers or ligands, markedly enhanced cell attachment onto the surface .…”

“…Courtenay et al incorporated the cationic trimethylammonium groups on the surface of cellulose scaffold by reaction with glycidyltrimethylammonium chloride and investigated the attachment of MG‐63 cells . They reported that a very small increase in the surface charge, without addition of any protein modifiers or ligands, markedly enhanced cell attachment onto the surface . In another study, Zhu and Fang found that fibroblast attachment was much stronger on the surface of positively charged chitosan substrates compared with negatively charged O ‐carboxymethyl chitosan scaffolds .…”

Scaffolds for 3D Cell Culture and Cellular Agriculture Applications Derived From Non-animal Sources

“…This observation will not necessarily extrapolate to other decellularized plant scaffolds due to their underlying native tissue geometry which makes plant species/tissue choice important (Gershlak et al, 2017). Although decellularization is depicted as a simple biomaterial development method, it lacks the customizability of "bottom-up" approaches, such as that of cellulose nanofibril scaffolds and cellulose composites with varying porosity, biological, and mechanical characteristics (Khan et al, 2016;Courtenay et al, 2017;Courtenay et al, 2018).…”